The purpose of this K24 application is to support the continuation and proposed expansions of Dr. Mallory Johnson's programs of mentoring and patient-oriented research (POR) in social and behavioral approaches to optimizing engagement in HIV care among drug-using populations. The candidate proposes new mentoring, new research, and additional training to build competency in drug abuse research, HCV and liver disease, and advanced research methodologies. The proposed plan for mentoring expands his current mentoring program in new directions, including an innovative grand mentoring program, new sources of mentees, development of online team-based mentoring tools, and scholarship in best practices of mentoring. These plans emphasize the importance of addressing challenges to successful transition to independence during periods of budgetary constraint through the leveraging and strategic use of data, infrastructure, and expertise available through existing NIH-funded research networks, training programs, and funding mechanisms. Three aims for new research are proposed, which will provide data for future interventions to improve health care empowerment and clinical outcomes for populations at risk for suboptimal engagement in HIV care, including HIV-infected substance users (men, women, and transgender women) and HIV/HCV co-infected women. These POR activities will be conducted within the infrastructure of the Women's Interagency Health Study (WIHS), the CFAR Network of Integrated Clinical Systems (CNICS) and a cohort of transgender women led by one of the candidate's mentees. The overriding theme of the new POR is to investigate the challenges of engagement in care and uptake, persistence, and adherence, to antiretroviral therapy (ART) among populations at greatest risk for poor treatment outcomes. These POR activities will involve active participation by mentees and will complement their development plans and transitions to independence. All of the new aims will be framed in the Model of Health Care Empowerment and will provide preliminary data for subsequent observational and interventional studies of engagement in care. Through the efficient leveraging of existing resources, collaborations, data, and affiliations with NIH-funded networks, the overarching goal of this application is to support the development of early career investigators, new mentors, and to provide opportunities for my own training/competency-building, and to catalyze new projects in the area of engagement in HIV care among at- risk populations.